The proposed studies will attempt to characterize and relate abnormalities in androge dynamics to the neoplastic process in the prostate gland. Efforts will be made to determine if these abnormalities are a simple consequence of aging or are linked to the process of neoplasia. The animals to be studied include normal dogs and senile dogs with benign prostatic hyperplasia (BPH). Normal and senile rats and guinea pigs, two species which appear to be free of prostatic neoplasms will also be compared to distinguish age-related changes from those related to neoplasia. In the proposed studies, the endogenous concentration of free and bound plasma testosterone (T) and dihydrotestosterone (DHT) will be measured by radioimmunoassay (RIA). Likewise, using RIA, the quantification of free and bound DHT in the cytosol and nuclei of the sex accessory glands will be attempted. The bound fraction of DHT in these glands will be isolated by sucrose density gradient techniques, and will represent that DHT which is selectively retained by prostatic androphiles. In addition, castration studies are planned to examine the rate of decline of endogenous T & DHT in normal and neoplastic sex accessory glands. This process may differ with neoplasia or aging. Such findings would suggest a possible difference in the half-life of plasma androgen(s) and would necessitate an analysis of this process. At the earliest near-maximal post-castrate decline in the endogenous androgen, the characteristics of the in vitro T-H3 uptake, and metabolism and DHT-H3 binding in nuclei and cytosol will be compared. This will be done in normal animals and senile animals possessing normal or neoplastic sex accessory glands. It is imperative that these processes be compared in the normal with this post-castrate interval. Removal of the complicating influence of the endogenous steroids via castration may reveal important differences between the mature and senile animals which may be otherwise obscured in the intact animal.